Inhibition of 2‐Amino‐1‐methyl‐6‐phenylimidazo [4,5‐b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure–Activity Relationship in a Model System

Abstract

The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure-activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect.

Inhibition of hazardous compound formation in muscle foods by antioxidative phytophenols

“…Some HAs are activated to genotoxicants in rat and human livers by cytochrome P450 (P450) 1A1‐ and 1A2‐mediated N ‐oxidation . The formation of HAs in food has been shown to involve free radicals, including ROS, that initiate oxidation processes, as well as pyrazine cation intermediate radicals . Chen et al .…”

“…As a diverse group of health-hazardous compounds, HAs have been identified in high-temperature processed foods, including grilled, baked, and fried meats, especially beef. 47 49,50 The formation of HAs in food has been shown to involve free radicals, 51,52 including ROS, that initiate oxidation processes, as well as pyrazine cation intermediate radicals. 53 Chen et al 54 reported that the reaction between creatinine and radicals of alkylpyridine led to the formation of MeIOx and IQ in fried ground beef.…”

Isorhamnetin and Hispidulin from Tamarix ramosissima Inhibit 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine (PhIP) Formation by Trapping Phenylacetaldehyde as a Key Mechanism

“…Third, the presence of the conjugated carbonyl group on the C ring increases the inhibitory effect of the three flavonoids on PhIP formation. Yu et al [22] also confirmed that the hydroxyl groups on the A ring of the detected flavonoids, particularly at the ortho positions (C-5 and C-7), inhibited PhIP formation to the greatest extent. The hydroxyl groups on the B and C rings of the flavonoids may exert a certain synergistic effect with the C-5 and C-7 hydroxyl groups on the A ring, which increased the inhibitory effect on PhIP formation.…”

“…When higher concentrations of isorhamnetin and hispidulin were added to the models, less PhIP was generated, in the study by Zhang et al [21], isorhamnetin is considered an effective inhibitor of PhIP formation in a model system, with an IC50 (50% inhibiting concentration) values of 1.675 mg/mL. In addition, Yu et al [22] analyzed the creatinine/phenylalanine chemical model system and reported an IC50 value of isorhamnetin of 2.246 mg/mL. Similar to the present study, 0.03 mmol isorhamnetin (0.95 mg/mL) showed an inhibitory rate of 57.84% and the minor difference may be due to the heating conditions and the concentrations of precursors.…”

Dual Effects of Creatinine on the Formation of 2‐Amino‐1‐Methyl‐6‐Phenylimidazo [4,5‐b]pyridine (PhIP)

“…The PhIP concentration was determined by HPLC‐MS/MS coupled with tandem solid‐phase extraction (Si‐SCX–2‐C 18 ; Zhang and others ; Yu and others ). The solutions were purified using Si‐SCX‐2 cartridges (500 mg, 6 mL; Silicycle Inc., Quebec, Canada) coupled to Hypersep C 18 cartridges (200 mg, 3 mL; Thermo Electron Corporation, Bellefonte, Pass., U.S.A.).…”